Transmission of cml or of t(9; 22) and bcr/abl? They are not the same

Access through your institution Buy or subscribe In a recent Letter to the Editor de Brito _et al._1 describe a transplant donor retrospectively found to have t(9;22) and _BCR/ABL_ along

with other cytogenetic abnormalities often associated with acute phase or blastic transformation of CML. There are several interesting points including: (1) the donor had normal blood

parameters and no evolution to chronic or acute phase CML for >6 months (but possibly several years) when t(9;22) and _BCR/ABL_ were detected in a substantial proportion of her myeloid

cells; (2) although the donor was chimeric for cells with and without t(9;22) and _BCR/ABL_, initial engraftment was with the normal donor cells; and (3) the recipient did not develop

chronic or acute phase CML after >6 months follow-up. Several points warrant consideration. First, it was reported many years ago that persons with chronic phase CML at diagnosis may have

CML cells with cytogenetic abnormalities consistent with acute phase.2 This is conceptually consistent with recent data from ultra-deep sequencing of the _BCR/ABL_ tyrosine kinase domain in

persons with chronic phase CML, where many mutations are identified before drug exposure.3 These data suggest a long latency from acquisition of _BCR/ABL_ to diagnosis of chronic phase CML.

Second, having _BCR/ABL_ is not equivalent to having CML. Data from several centres report normal persons with _BCR/ABL_.4 The point is that to have CML the _BCR/ABL_ mutation must be in a

cell biologically capable of causing the disease. Whether this was so in this donor (and/or recipient) is unknown. Consequently, starting CML therapy may have been premature and/or

unnecessary, especially absent data-treating chronic phase CML earlier is of benefit. Third, latency from _BCR/ABL_ to developing CML is unknown and likely highly variable. The common notion

derived from the A-bomb survivors of 10–15 years latency is probably wrong. Some children with typical CML, t(9;22) and _BCR/ABL_, were diagnosed before age 1 year and have a somatic

(acquired) mutation implying CML latency can be<2 years. Also, our and other reviews of the A-bomb data suggest an early peak of CML may have occurred<5 years and even<2 years after

exposure.5 Organised surveillance of CML risk did not begin until about 10 years after the A-bomb exposures. More importantly, an increased CML-risk persisted in exposed persons for up to

40 years.6 Based on these data and the ages of donor and recipient, they may never have developed CML in their lifetimes. We do not fault de Brito _et al._ for treating these persons but it

may have been unnecessary. Certainly it would have been interesting to follow these persons to determine if they developed CML. A final point is CML cells do not always have a substantial

growth advantage over normal myeloid cells, which is often used to explain why the chronic phase CML clone eventually displaces (or replaces) normal haematopoietic cells. In this case

initial engraftment was with normal donor cells followed by appearance of cells from the CML clone but no clinical features of CML for >6 months. This is a preview of subscription

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support REFERENCES * de Brito MD, Campilho F, Branca R, Vaz CP, Campos A . Inadvertent transmission of occult CML through allo-SCT. _Bone Marrow Transplant_ 2015; 50: 598. Article  CAS 

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AUTHORS AND AFFILIATIONS * Division of Experimental Medicine, Department of Medicine, Haematology Research Centre, Imperial College London, London, UK R P Gale & J F Apperley Authors * R

P Gale View author publications You can also search for this author inPubMed Google Scholar * J F Apperley View author publications You can also search for this author inPubMed Google

Scholar CORRESPONDING AUTHOR Correspondence to R P Gale. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of Interest. RIGHTS AND PERMISSIONS Reprints and permissions

ABOUT THIS ARTICLE CITE THIS ARTICLE Gale, R., Apperley, J. Transmission of CML or of t(9; 22) and _BCR/ABL_? They are not the same. _Bone Marrow Transplant_ 50, 1582 (2015).

https://doi.org/10.1038/bmt.2015.199 Download citation * Published: 14 September 2015 * Issue Date: December 2015 * DOI: https://doi.org/10.1038/bmt.2015.199 SHARE THIS ARTICLE Anyone you

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